Fast Acquisition of Proton-Detected HETCOR Solid-State NMR Spectra of Quadrupolar Nuclei and Rapid Measurement of NH Bond Lengths by Frequency Selective HMQC and RESPDOR Pulse Sequences

Abstract

Fast magic-angle spinning (MAS), frequency selective (FS) heteronuclear multiple quantum coherence (HMQC) experiments which function in an analogous manner to solution SOFAST HMQC NMR experiments, are demonstrated. Fast MAS enables efficient FS excitation of ¹ H solid-state NMR signals. Selective excitation and observation preserves ¹ H magnetization, leading to a significant shortening of the optimal inter-scan delay. Dipolar and scalar ¹ H{¹⁴ N} FS HMQC solid-state NMR experiments routinely provide 4- to 9-fold reductions in experiment times as compared to conventional ¹ H{¹⁴ N} HMQC solid-state NMR experiments. ¹ H{¹⁴ N} FS resonance-echo saturation-pulse double-resonance (RESPDOR) allowed dipolar dephasing curves to be obtained in minutes, enabling the rapid determination of NH dipolar coupling constants and internuclear distances. ¹ H{¹⁴ N} FS RESPDOR was used to assign multicomponent active pharmaceutical ingredients (APIs) as salts or cocrystals. FS HMQC also provided enhanced sensitivity for ¹ H{¹⁷ O} and ¹ H{³⁵ Cl} HMQC experiments on ¹⁷ O-labeled Fmoc-alanine and histidine hydrochloride monohydrate, respectively. FS HMQC and FS RESPDOR experiments will provide access to valuable structural constraints from materials that are challenging to study due to unfavorable relaxation times or dilution of the nuclei of interest.

Keywords: NMR crystallography; fast magic angle spinning; pulse sequences; structure determination.